Screen to identify an osteoblast membrane receptor and its functional analysis

• Project/Area Number: 25670142
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Osaka University
• Principal Investigator: FURUKAWA Takahisa 大阪大学, たんぱく質研究所, 教授 (50260609)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Obif / 骨芽細胞 / 軟骨細胞 / 骨粗鬆症 / 骨芽細胞分化誘導能 / Obif受容体

Outline of Final Research Achievements

Osteoporosis is one of the most important theme to be solved in a rapidly aging society. We screened genes regulating chondrocyte differentiation, and identified Obif, a single transmembrane protein, and Cfm2, which is highly expressed in proliferating and prehypertrophic chondrocytes. We generated Cfm1/Cfm2 double-knockout (Cfm DKO) mice. The number of cartilaginous cells in intervertebral discs is remarkably reduced, and chondrocytes are moderately reduced in Cfm DKO mice. In addition to interaction between Cfm and Filamin proteins, we showed that Cfm is required for the interaction between Flnb and Smad3. Multiple lines of evidence reported mutational congenital anomalies of Flnb including autosomal recessive spondylocarpotarsal syndrome, autosomal dominant boomerang dysplasia, Larsen syndrome, and atelosteogenesis I and III phenotypes. This study is expected to accelerate the development of novel diagnosis and cure methods for congenital skeletal malformation in the future.

Research Products

• [Journal Article] Filamin-interacting proteins, Cfm1 and Cfm2, are essential for the formation of cartilaginous skeletal elements. (2014)
  • Author(s): Mizuhashi K, Kanamoto T, Moriishi T, Muranishi Y, Miyazaki T, Terada K, Omori Y, Ito M, Komori T, Furukawa T.
  • Journal Title: Human molecular genetics Volume: - Issue: 11 Pages: 2953-2967
  • DOI: 10.1093/hmg/ddu007
  • Peer Reviewed / Open Access
• [Journal Article] Filamin-interacting proteins, Cfm1 and Cfm2, are essential for the formation of cartilaginous skeletal elements. (2014)
  • Author(s): Mizuhashi K, Kanamoto T, Moriishi T, Muranishi Y, Miyazaki T, Terada K, Omori Y, Ito M, Komori T & Furukawa T.
  • Journal Title: Human Molecular Genetics Volume: -
  • Peer Reviewed